Determination of the sulphoxides and sulphones of three simple sulphides in rat urine: effects of phenobarbitone, β ‐naphthoflavone and methimazole

In this investigation, the measurement and identication of the S ‐oxidation products of three simple sulphides—ethyl methyl sulphide (EMS), 4‐chlorophenyl methyl sulphide (CPMS) and diphenyl sulphide (DPS)—in rat urine were carried out and a study of the effects of phenobarbitone (PB), β ‐naphthoavone ( β NF) and methimazole on the urinary levels of their metabolites was conducted. Male Wistar rats ( n = 4) were pretreated with PB (80 mg/kg/day in saline, i.p.), β NF (100 mg/kg/day in corn oil, i.p.), methimazole (50 mg/kg/day in saline, i.p.) or the vehicles alone (1 mL/kg) for three consecutive days. After pretreatment, EMS, CPMS or DPS (50 mg/kg in corn oil, 500 µL) was administered orally to the appropriate groups of rats. The animals were placed in metabolic cages and urine samples collected at 24 h intervals over 96 h. Chromatographic and spectroscopic techniques were used for the measurement and identication of the sulphoxides and sulphones of EMS, CPMS and DPS in rat urine. Although only a trace of ethyl methyl sulphoxide (EMSO) was present in rat urine after administration of EMS, ethyl methyl sulphone (EMSO 2 ) accounted for about 16% of the administered dose in the urine of male rats given EMS. In addition, pretreatment of rats with methimazole signicantly decreased the S ‐oxidation of EMS. 4‐Chlorophenyl methyl sulphone (CPMSO 2 ) was the main metabolite recovered in the urine of male rats treated with CPMS, accounting for about 10% of the dose. Pretreatment of rats with PB before administration of CPMS signicantly increased the levels of CPMSO 2 excreted in the urine. Additionally, pretreatment of rats with methimazole signicantly decreased the S ‐oxidation of CPMS in vivo . About 2.5% of diphenyl sulphoxide (DPSO) and 4% of diphenyl sulphone (DPSO 2 ) were recovered in the urine of male rats given DPS. Pretreatment of rats with PB, β NF or methimazole before administration of DPS decreased the levels of DPSO and DPSO 2 excreted in the urine, although this was not statistically signicant. These results indicate that microsomal monooxygenases mediate the S ‐oxidation of EMS, CPMS and DPS to their corresponding sulphones via a transient sulphoxide in rats. Copyright © 2004 John Wiley & Sons, Ltd.